Nanoparticles are those particles having one or more dimensions of the order of 100 nm or less. Nanoparticles can have different sizes and it is known for a specific type of nanoparticle to have varying size dimensions. It is also known to grow larger nanoparticles from smaller nanoparticles. Growth of individual NPs is usually by addition of atomic/molecular scale components. This can be done either by adding precursor material (seed mediated growth) to the NP suspension in which case there are the same number of nanoparticles at the end of the process as there were at the beginning, or by adding NPs to the NP suspension (Ostwald ripening). In the latter process one set of NPs act as a source of atomic/molecular scale components and that material is then added to the growing NPs In both these processes there is no aggregation of individual nanoparticles. Providing a plurality of individual single nanoparticles of different sizes is different to providing clusters of nanoparticles or nanoparticle clusters. A nanoparticle cluster is the result of two or more nanoparticles binding to one another through a physical or chemical interaction, with the resultant entity being a combination of the two or more individual nanoparticles such that the plurality persists for a timescale long in comparison to the atomic/molecular time scales associated with the process that result in the combination. Within a cluster, it is possible to identify the individual nanoparticles.
Stable suspensions of magnetic nanoparticles (NPs) and of magnetic nanoparticle clusters (NPCs) have great potential biomedical applications. They have been considered as potential drug delivery vehicles which can be localized at a site of interest by application of external magnetic fields. They are currently also being used as contrast agents for magnetic resonance imaging (MRI) as the large magnetic moments, associated in particular with iron-oxide NPs, produce strong magnetic resonance relaxation enhancements which can be used to improve image contrast in body tissues containing the agent.
Despite these beneficial applications, significant challenges remain to fully exploit this biomedical potential. Amongst these are improvement in the control of cluster size, composition and architecture, as these properties largely determine the cluster bio-distribution, drug delivery potential and the molar MRI relaxation rate enhancements (the spin-lattice and spin-spin relaxivities, r1 and r2).
Methods for preparing magnetic NPCs include the reaction of primary NPs with polymers and in situ NP formation and stabilization. In the former approach the surface chemistry of the polymer determines the outcome and so for a given polymer, stable suspensions can usually only be produced at one cluster size, while larger clusters are associated with low NP loading.
A common approach to improve the functionality and stability of magnetic NPs and NPCs is to incorporate noble metals, particularly gold, as Au/FeO nanocomposite materials. The most common architecture involves coating FeO cores in a complete layer, or shell, of gold, producing FeO@Au nanoparticles. The gold shell imparts many favourable properties, largely due to the well established Au—S chemistry, which offers the possibility of conjugating hydrophilic ligands and bioactive molecules. However, control of the thickness of the Au layer remains a challenge and the layer reduces the saturation magnetization of the particles, which greatly reduces the contrast agent potential of core-shell materials.
The preparation of Au NPs conjugated to FeO NPs has also been reported. Negatively charged, 2-3 nm, Au NPs were chemically attached onto amino-siloxane (APTES) coated ˜10 nm Fe3O4 nanoparticles, producing stable ethanol suspensions. This approach was demonstrated to have minimal effect on the saturation magnetization. For application as T2 contrast agents, or as drug delivery vehicles, further steps involving controlled assembly of such particles would be necessary.
There is therefore a need to provide improved mechanisms for providing nanoparticle clusters.